Monday, December 10, 2007

SEED and the Central Dogma of Molecular Biology - I Take Back My Praise

On October 1, 2007 I praised SEED magazine for being one of the few science magazines to correctly define the Central Dogma of Molecular Biology. Here's what I said two months ago.

One of my pet peeves is the misuse of the term "Central Dogma of Molecular Biology" [Basic Concepts: The Central Dogma of Molecular Biology]. Most people define it as the flow of information from DNA to RNA to protein. Many then go on to declare that the Central Dogma has been overthrown because of reverse transcriptase, alternative splicing, microRNA, epigenetics, or whatever.

This month's issue of SEED has a tear-out summary (cribsheet) of "Genetics." In one of the boxes titled "The Central Dogma of Molecular Biology" there's a drawing of the major pathways of information flow [Cribsheet #12]. The caption says.

There are nine ways information can theoretically flow between DNA, RNA, and protein. Of these, three are seen throughout nature, DNA to DNA (replication), DNA to RNA (transcription), and RNA to protein (translation). Three more are known to occur in special circumstances like viruses or laboratory experiments (RNA to RNA, RNA to DNA, and DNA to protein). Flows of information from protein have not been observed. The trend is clear: information flow from DNA or RNA into protein is irreversible. This is known as the "central dogma," and forms the foundation of molecular biology.

Yeah! As far as I know this is the only popular magazine to get it right.

I take it all back.

This month's issue has an article by Philip Ball outlining another revolution in molecular biology that overthrows the Central Dogma of Molecular Biology. This time it's microRNAs that have done the dirty deed [Redefining Genes].

Philip Ball is a London (UK) based freelance science writer with a Ph.D. in Physics. He has written 10 books on science and many articles for the news section of Nature. Philip Ball blogs at homunculus.

Here's what he says on page 29 of the current newsstand issue of SEED.

For nearly 50 years, the central dogma of molecular biology has been that genetic information is contained within DNA and is passed by rote transcription through RNA to make proteins. ...

The central dogma is being eroded, and it now appears as if DNA's cousin, the humble intermediary RNA, plays at least an equal role in genetics and the evolution of the species.

Philip Ball then gives two recent examples of work showing the involvement of noncoding RNA in gene expression. Then comes the revolution ...

These and a host of other recent findings are rewriting the textbooks of molecular biology. They are beginning to show not only that RNA is more fundamental to genetics than once believed, but also that it can directly affect evolution and elucidate the differences between species. The result is a story that looks a lot messier, but potentially a lot more interesting, than anyone ever guessed.

This is deeply insulting to all biochemists and molecular biologists. What in the world must people like Ball be thinking of us when he writes such nonsense? Does he really believe that for over half a century we have been slavishly adhering to the dogma that genes only make proteins? I know lots of scientists who think the Central Dogma refers to the general pathway of information flow (DNA → RNA → protein) but I never met a biochemist or a molecular biologist who thought that this pathway ruled out genes whose final product was RNA.

That idea is total nonsense, of course, and Philip Ball would know this if he only bothered to read any of the textbooks of molecular biology. Not only have we been teaching about ribosomal RNA, and transfer RNA for 40 years, we've also covered all of the small RNAs involved in splicing, telomeres, signal recognition particle, RNAse P etc. etc. Does he think we're completely ignorant of the Nobel Prizes awarded to Sidney Altman and Tom Czech in 1989 "for their discovery of catalytic properties of RNA"?

Furthermore, we've been teaching about regulatory RNAs for almost as long. The classic examples are the antisense RNAs in bacteriophage λ, attenuation in the trp operon and small RNAs that control the initiation of DNA replication at plasmid origins.

If you were to believe Philip Ball, molecular biologists have clung to his version of the Central Dogma of Molecular Biology in spite of all these counter-examples. Only now are they waking up to the fact that some genes make RNA as their final product. How stupid is that?

Science writers have a special obligation when writing for a general audience. Not only do they have to explain things in simple language but they have to be accurate as well. Pert of being accurate in science is having enough knowledge of the subject to be able to sort out the hype from reality. Philip Ball does not know anough about molecular biology to make that call. He should have read the cribsheet.

10 comments:

At U of T, I haven't taken a single course that presented the Central Dogma correctly. Everybody (except you, obviously) seems to think it's DNA-->RNA-->protein.

For example, Malcolm Campbell got it wrong in BIO250. The course website is http://bio250y.chass.utoronto.ca; go to Lectures (on left hand side); Part 2; and look at lecture 1, slides 2 and 3. He is of the opinion that the "central dogma" is wrong and needs to be "elaborated" upon.

The central dogma of molecular biology was first enunciated by Francis Crick in 1958[1] and re-stated in a Nature paper published in 1970:[2]

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid.

In other words, 'once information gets into protein, it can't flow back to nucleic acid.'

Interestingly, answers.com have the above definition listed under 'central dogma (molecular biology)', but the following definition listed under 'central dogma (genetics)':

The concept, subject to several exceptions, that genetic information is coded in self-replicating deoxyribonucleic acid and undergoes unidirectional transfer to messenger ribonucleic acids in transcription that act as templates for protein synthesis in translation.

At U of T, I haven't taken a single course that presented the Central Dogma correctly. Everybody (except you, obviously) seems to think it's DNA-->RNA-->protein.

That's pretty sad, isn't it? What it shows you is that your Professors are just copying from the textbooks without doing any checking on their own.

It's especially sad when they go on to say that the "Central Dogma of Molecular Biology" is wrong! That's totally illogical. Either it really is a correct central dogma, in which case their definition must be wrong, or it's an incorrect central dogma, in which case molecular biologists must be idiots.

Normally when faced with such a paradox you'd expect scientists to do a bit of research on the Central Dogma of Molecular Biology. It's not that hard—if you Google "Central Dogma of Molecular Biology" you find that the top three results are wrong but the fourth leads you to Crick's original paper. (The fifth brings you here.)

I remember I was taught it incorrectly in undergrad and in graduate school. I misquoted it myself and a commenter pointed me to your explanation, so I finally have it right - shortly before receiving a PhD in molecular physiology.

It's a problem in science. We tend to get taught a narrow window of science, and the correct history is underemphasized in the rush to teach you to hold a pipette.

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Some readers of this blog may be under the impression that my personal opinions represent the official position of Canada, the Province of Ontario, the City of Toronto, the University of Toronto, the Faculty of Medicine, or the Department of Biochemistry. All of these institutions, plus every single one of my colleagues, students, friends, and relatives, want you to know that I do not speak for them. You should also know that they don't speak for me.

Superstition

Quotations

The old argument of design in nature, as given by Paley, which formerlyseemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.

Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.

The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.

Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.

The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.